Distinct biological differences (growth efficiency, transformation) between endogenous and exogenous avian retroviruses were correlated with genomic sequence differences present between these two virus groups. It was found that 1) the viral 3' end (c region) is the single most important determinant of virus growth, and (2) a short sequence close to the 5' end of the viral genome and another sequence between the env and src genes play a control role in the expression of the function of the transforming gene src. We are now involved in work which aims to a more detailed understanding of the functions of these genetic regions and to the examination of their potential involvement in leukemogenesis by nontransforming type-c retroviruses.